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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 307 records · Page 17Linked to original sources
PubMed2000

Heterogeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels.

Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones), including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring <10 microm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A- and C-zones, and measuring up to 40 microm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.

Adult↗
PubMed2000

Antibody reactivity to Cryptosporidium parvum in saliva of calves after experimental infection.

Antibodies against Cryptosporidium parvum in the saliva and sera of three calves experimentally infected with this parasite were examined by an indirect immunofluorescence antibody test and immunoblotting. Salivary anti-C. parvum IgA antibody appeared on day 12 post-challenge and had a tendency to increase transiently between days 15 and 30 post-challenge. Salivary anti-C. parvum IgG antibody levels showed a gradual increase along with the change in IgA antibody levels during the infection. In contrast, serum anti-C. parvum IgA antibody levels showed only a slight increase between days 15 and 30 post-challenge. Serum anti-C. parvum IgG antibody levels rose on day 12 post-challenge and one calf maintained relatively high level up to the end of the experiment. In immunoblotting, an antigen with a molecular mass of 15 kDa was found to react strongly to salivary IgA antibody and a 27 kDa antigen to react to serum IgG antibody.

Animals↗
PubMed2000

Coronary atherosclerosis in youths in Kyushu Island, Japan: histological findings and stenosis.

We histologically examined the coronary arteries of 52 autopsied cases of the youths (3 to 39 years of age, mean 28.5 years) in Kyushu island, Japan, without clinical events of coronary artery diseases. The coronary artery specimens were taken from the proximal portions of the right coronary artery (Seg. 1), the left anterior descending artery (Seg. 6), and the macroscopically most stenotic region (ST). Atherosclerotic lesions were histologically classified into four types: concentric fibrous, eccentric fibrous, concentric lipid rich, or eccentric lipid-rich type. The degrees of stenosis (< 25%, 25-50%, 50 75%, > 75%) were morphometrically evaluated. The majority of coronary arteries with under 50% stenosis were of the concentric fibrous type. Lipid-rich types of coronary atherosclerosis increased in the coronary arteries with over 50% stenosis and were observed in the Seg. 6 and ST, while 70% of Seg. 1 lesions with over 50% stenosis were of a fibrous type. Serum cholesterol levels of patients with a lipid rich type of coronary atherosclerosis were significantly higher than those with a fibrous type. These results suggested that the early stage of coronary atherosclerosis in Japanese youths is mainly of a concentric fibrous type, which later develops to a lipid rich type. Hypercholesterolemia would promote the progression of atherosclerosis.

Adolescent↗
PubMed2000

Role for activation of matrix metalloproteinases in the pathogenesis of pulmonary lymphangioleiomyomatosis.

BACKGROUND: Matrix metalloproteinases (MMPs) have been shown to be involved in the pathogenesis of the destructive pulmonary lesions in patients with lymphangioleiomyomatosis (LAM); in the present report, the activation of these enzymes is examined. OBJECTIVE: To evaluate the role of MMPs and their activating enzymes, immunohistochemical and confocalmicroscopic techniques were used to localize alpha-smooth muscle actin (alpha-SMA), HMB-45, proliferating cell nuclear antigen (PCNA), MMP-2, membrane-type 1 MMP (MT1-MMP), MT2-MMP, and MT3-MMP in lung tissues from 10 women with LAM. Tissue samples were obtained from 5 patients before treatment and in 5 patients after hormone treatment (progesterone and/or tamoxifen citrate). RESULTS: Staining for alpha-SMA and MMP-2 was present in all the abnormal smooth muscle cells (LAM cells) in both groups. The percentages of PCNA-, MMP-2-, or MT1-MMP-positive LAM cells were much higher in the untreated group than in the treated group, whereas the percentages of HMB-45-reactive LAM cells were similar in both groups. The reactions for MT1-MMP and PCNA were preferentially localized in small spindle-shaped LAM cells; the reaction for HMB-45 was found in large epithelioid LAM cells. Many of the PCNA-positive cells were also positive for MT1-MMP. Staining for MT2-MMP and MT3-MMP was negative. CONCLUSIONS: This study demonstrates an association between cellular proliferation and the presence of MT1-MMP in LAM cells. The activation of MMP-2 by MT1-MMP may play an important role in the destruction of lung tissue in this disorder.

Actins↗
PubMed2000

Hyperplasia of type II pneumocytes in pulmonary lymphangioleiomyomatosis.

BACKGROUND: Little is known of the morphology of the pneumocytes lining the parenchymal cysts in lymphangioleiomyomatosis (LAM). OBJECTIVE: To evaluate the structural characteristics of the alveolar epithelial cells in LAM. METHODS: Immunohistochemical and electron microscopic studies were performed on lung tissue from 22 women with pulmonary LAM. RESULTS: Epithelial cells that reacted with PE-10 (a mouse monoclonal antibody that recognizes the surfactant apoprotein A in type II pneumocytes) and TTF-1 (an antibody that identifies nuclear transcription factor found in type II pneumocytes) were the predominant cell type lining the surfaces of lesions of LAM and normal areas of lung. Scanning and transmission electron microscopic studies confirmed that these cells were type II pneumocytes as demonstrated by (1) apical microvilli, (2) electron-dense lamellar bodies, and (3) cytoplasmic projections that extended from the basal surfaces into the underlying connective tissue, where they made extensive contact with interstitial connective tissue cells. A few cells had morphologic characteristics of type I pneumocytes, including large flat surfaces lacking microvilli. Cells that appeared intermediate between type I and type II pneumocytes were observed occasionally. CONCLUSIONS: These observations and the reactivity of these cells with antibody to proliferating cell nuclear antigen demonstrate that extensive hyperplasia of type II pneumocytes is a major characteristic of LAM.

Adult↗
PubMed2000

[The role of preoperative staging for pancreatic cancer].

Despite the poor prognosis of pancreatic carcinoma patients, surgical resection remains the only potentially curative treatment. As it has been demonstrated that extended radical surgery does not lead to a better prognosis, accurate staging to select those patients who may benefit from resection is essential. According to the report of a national survey of pancreatic cancer in 1997, patients with S0 or S1, RP0 or RP1, and N0 or N1 disease have longer survival periods compared with patients with S2, RP2, and N2 disease. Therefore patients classified as Stage I, Stage II, or Stage III are recognized as candidates for surgical resection. Patients classified as Stage IVb because of positive P factor or positive H factor are selected for conservative treatment such as chemotherapy and irradiation. It remains to be clarified whether patients classified as Stage IVa should undergo surgical resection or not. Future prospective randomized studies of patients with Stage IVa disease will reveal whether surgical resection or chemoradiation is effective. Helical CT is useful to evaluate S and RP factors for definitive preoperative staging. CT-AP can reveal occult metastases to the liver. These preoperative evaluations should be evaluated along with histological findings.

Humans↗
PubMed2000

Ethanol patch test: a simple method for identifying the effectiveness of cyanamide in alcoholics.

BACKGROUND: To identify the pharmacological effectiveness of cyanamide, 144 alcoholics treated with cyanamide were subjected to a test that used an acetaldehyde dehydrogenase (ALDH) inhibitor, the ethanol patch test, which is considered to be a good indicator of ALDH2 phenotype. METHODS: We placed 100 microl of 70% ethanol on a lint pad and, as a control, placed the same volume of distilled water on a second pad. The ethanol patch test was performed on 144 alcoholics more than 2 weeks after abstinence from alcohol before and after treatment with cyanamide for 1 week. The dose of cyanamide was increased up to 150 mg until the patch test yielded a positive result. RESULTS: In the ethanol patch test, 36 alcoholics (25.0%) gave a positive result before treatment with cyanamide and might have been ALDH2(1)/2(2) heterozygotes. Among 108 alcoholics who were not positive, the distribution of the cyanamide dose that yielded a positive ethanol patch test result was 30 mg in 42 cases (38.9%), 50 mg in 33 cases (30.6%), 70 mg in 5 cases (4.6%), 100 mg in 6 cases (5.6%), and 150 mg in 2 cases (1.9%). Prevalence of liver cirrhosis was significantly higher in alcoholics who showed a positive ethanol patch test result at doses of less than 50 mg cyanamide than those at doses more than 70 mg (p = 0.029). The prevalence of adverse effects was significantly higher in alcoholics who showed a positive ethanol patch test result at doses of more than 70 mg than at doses of less than 50 mg cyanamide (p = 0.002). CONCLUSIONS: The ethanol patch test is a useful method for identifying pharmacological effectiveness of cyanamide and may reduce the prevalence of side effects in cyanamide-treated alcoholics.

Adult↗
PubMed2000

Rifampicin suppresses hepatic CYP2E1 expression and minimizes DNA injury caused by carbon tetrachloride in perivenular hepatocytes of mice.

BACKGROUND: Rifampicin has been shown to increase during activities of serum transaminases and to decrease in cytochrome P-450-mediated monooxygenase activities in livers of mice treated with carbon tetrachloride (CCl4). Although these findings suggest that rifampicin prevents hepatocyte damage caused by CCl4, detailed information on the protective effects is not available. METHODS: We injected first rifampicin and then CCl4 into mice and examined denaturation and fragmentation of hepatocyte DNA by in situ nick translation, in situ end labeling, and in situ hybridization. Furthermore, expressions of p53, a cytoplasmic marker for apoptosis, and bcl2, an anticell death factor, were examined immunohistochemically. In addition, a major ethanol-inducible P-450 isoform in liver homogenates or microsomes, CYP2E1, was examined by Western blotting, because the enzyme metabolizes CCl4 and forms free radicals to injure perivenular hepatocytes in which the enzyme is restrictedly expressed. RESULTS: Rifampicin prevented the denaturation and fragmentation of DNA caused by CCl4 in perivenular hepatocytes except for those located within two or three cell layers surrounding the central venule. Furthermore, CYP2E1 decreased in liver homogenates or microsomes from rifampicin-treated animals. It is therefore likely that rifampicin suppresses expression of CYP2E1 and protects CCl4-mediated DNA damage of hepatocytes by inhibiting formation of free radicals. In addition, perivenular hepatocytes except for those surrounding the venule showed negative immunoreaction for p53 and bcl2 in rifampicin+CCl4-treated animals. CONCLUSIONS: The drug did not alter the mechanism of cell death from necrosis to apoptosis and did not promote recovery of hepatocytes from CCl4-mediated damage.

Animals↗
PubMed2000

[A case of sarcoid myopaty with external ocular muscle involvement--diagnosis and follow-up study with 99mTc pyrophosphate scintigraphy].

A 62-year-old woman was admitted to our hospital because of diplopia and muscular weakness. She had been diagnosed as having sarcoidosis histologically by skin biopsy 5 years before. Although neither CT nor MRI could detect the granulomas, 99mTc-pyrophosphate scintigraphy successfully detected the involvement of sarcoidosis not only in the skeletal muscles but also in the external ocular muscles. After treatment with prednisolone, the symptoms markedly subsided and increased uptake of radionucleotide disappeared. Although 67Ga scintigraphy is also known to be useful in investigating the sites affected by sarcoidosis throughout the body, it was not effective in detecting the involvement of external ocular muscle due to the physiological uptake of 67Ga to the lacrimal grands. While the granulomas are frequently observed histologically in skeletal muscles, usually they are not associated with muscle symptoms. In our study 99mTc-pyrophosphate scintigraphy has proven to be useful in investigating the nodular lesions in skeletal muscles of sarcoidosis than 67Ga scintigraphy.

Female↗
PubMed2000

[Treatment of renal cell carcinoma extending into the right atrium with extra-corporeal circulation using high-grade hypothermia: a case report].

A 68-year-old woman underwent surgical treatment for renal cell carcinoma associated with tumor thrombus extending into the right atrium. Although the tumor thrombus reached the level of the right atrium, there were no other apparent metastases. Combination therapy with interferon alfa plus tegafur/uracil (UFT) was attempted with the expectation of reducing the tumor thrombus, but there was no change. Successful management was achieved with right radical nephrectomy, right auriculotomy, and partial cavectomy using cardiopulmonary bypass under high-grade hypothermia. After removal of the tumor and thrombus, blood loss was 13,900 ml during the patient's recovery. She had mild heart failure for about two weeks after the operation, but recovered. She was discharged on the 40th day after the operation. Proper preparation for blood transfusion is the key point of this operation.

Aged↗
PubMed2000

[Assessment of most appropriate background subtraction method for quantification of 123I-metaiodobenzylguanidine (MIBG) myocardial uptake by comparing with plasma ANP and BNP].

BACKGROUND: Quantification of 123I-metaiodobenzylguanidine (MIBG) myocardial uptake is widely accepted as a useful tool for estimating the severity of congestive heart failure. However, most reliable method has not been determined yet because of the difficulty of background (BG) subtraction. In this study, the most appropriate BG subtraction method was evaluated as compared with plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine (NEP) and left ventricular ejection fraction (LVEF). METHODS: Twenty-one patients with chronic heart failure were examined. After bolus injection of 123I-MIBG (111 MBq), dynamic anterior chest images were collected every second for 2 minutes. Planar anterior chest images were obtained 15 minutes (early image) and 4 hours later (delayed image) respectively. The parameters for quantification of 123I-MIBG myocardial uptake used in this study were heart to mediastinum ratio (H/M), myocardial washout rate and uptake ratio. Background was calculated using the region of interest (ROI) placed over a part of upper mediastinum, whole upper mediastinum, right lung and pericardial space respectively. The values of these parameters were calculated with and without BG subtraction and compared with plasma ANP, BNP and others. RESULTS: H/M did not correlate with ANP or BNP. Myocardial washout rate without BG subtraction showed significant correlation with ANP (p < 0.01) and BNP (p < 0.05). After BG subtraction employing ROI placed over the part of upper mediastinum and whole upper mediastinum, myocardial washout rate showed better correlation with BNP (p < 0.01). Myocardial uptake ratio did not showed any correlation with ANP or BNP without BG subtraction. However, myocardial uptake ratio showed significant correlation with BNP (p < 0.05) after subtraction of upper mediastinal BG. BG subtraction using ROI over right lung or pericardial area revealed poor results in both myocardial washout rate- and uptake ratio. CONCLUSION: BG subtraction using ROI over the upper mediastinum is likely to be suitable for quantitative analysis of 123I-MIBG myocardial scintigram.

3-Iodobenzylguanidine↗
PubMed2000

Phase I trial of oral 2'-deoxy-2'-methylidenecytidine: on a daily x 14-day schedule.

2'-deoxy-2'-methylidenecytidine (DMDC) is a potent deoxycytidine analogue. Preclinical studies of DMDC demonstrated activity against a variety of murine and human tumors in cell cultures and murine models and indicate enhanced antitumor activity of DMDC when it was administered in a manner that provided prolonged systemic exposure. In view of this observation, this study was designed to determine the toxicities, maximum-tolerated dose, and pharmacokinetic profile of DMDC. DMDC was given p.o. under fasting conditions for 14 consecutive days every 4 weeks in patients with advanced solid tumors. The starting dose was 12 mg/m2/day. Pharmacokinetic studies were carried out on days 1 and 14 of the first cycle. Fourteen patients received 22 courses of DMDC. The dose-limiting toxicities were anorexia, leukopenia, thrombocytopenia, and anemia. General fatigue was the common nonhematological toxicity. The maximum-tolerated dose was 18 mg/m2/day, at which two of six patients developed grade 3 toxicities. This dose level could also be considered for Phase II testing with this schedule. At the 18-mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), the area under the plasma drug concentration-time curve (AUC(0-infinity)) on day 1 were 1.7496 h, 112.9 ng/ml, and 399.8 ng x h/ml, respectively. Forty to 50% of the administered dose was recovered in the urine, indicating a good bioavailability and resulting significant systemic exposure to the drug, which may enable chronic oral treatment.

Adenocarcinoma↗
PubMed2000

[Molecular defects in hormone receptors and G proteins in human disorders].

The biological effects of hormones are mediated by plasma membrane and nuclear receptors which transmit extracellular signals to the cytoplasm and nucleus. The mutations in these receptors can affect normal signal transduction with loss-of-function mutations leading to hormone resistance and gain-of-function mutations leading to constitutive activation of signaling pathways. Mutations in plasma membrane are involved in a large number of clinical disorders, including dwarfism, Laron syndrome, congenital hyperthyroidism or hypothyroidism, nephrogenic diabetes insipidus, resistance to TSH, LH, FSH and ACTH, Jansen's metaphyseal chondrodysplasia and autosomal dominant hypoparathyroidism. While, mutations in nuclear receptors are the cause of resistance to glucocorticoid, androgen, estrogen, thyroid hormone and vitamin D. The loss-of-function mutations leading to familial hormone resistance disorders are germ line in origin whereas the gain-of-function mutations leading to constitutively active receptors are somatic. The plasma membrane receptors for those disorders except GH resistance consist of seven spanning-transmembranes which couple with GTP binding (G) protein. Abnormal G protein also exhibits gain and loss of function for hormones, leading to tumors and pseudo-hypoparathyroidism, respectively. This review summarizes molecular defects in hormone receptors and G proteins and their associated clinical features.

Cell Membrane↗
PubMed2000

Morphological and cytogenetic changes in therapy-related leukemia developed in a t(8;21)-acute myeloid leukemia (M2) patient: sequential cytogenetic and molecular analyses.

A patient with acute myeloid leukemia (AML)-M2 with t(8;21)(q22;q22) achieved complete remission with remission-induction chemotherapy followed by consolidation and intensification chemotherapies. T(8;21)(q22;q22) disappeared, but chimeric AML1/MTG8 was continuously detected in bone marrow cells. Following the development of therapy-related leukemia after 1 year, evolution of therapy-related AML-M4 with t(11;17)(q23;q25) and the rearrangement of the MLL gene were observed, while AML/MTG8 disappeared. After reinduction and following intermittent chemotherapies, a subsequent alternative transformation to AML-M2 occurred after detection of t(3;21)(q21;q22), with a break in the AML1 gene shown by interphase fluorescence in situ hybridization analysis. This leukemia transformed to AML-M4 after t(9;22)(q34;q11), with a minor BCR/ABL rearrangement, and then finally to AML-M2. This therapy-related leukemia was resistant to chemotherapy. These findings indicate that alterations in cytogenetic and molecular events caused by chemotherapeutic agents contribute to the sequential evolution of new leukemic clones with different morphology.

Adult↗
PubMed2000

Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity.

BACKGROUND: Interferon (IFN)-gamma is a key to protective immunity against a variety of intracellular bacterial infections, including Chlamydia trachomatis. Interleukin (IL)-18, a recently identified Th1 cytokine, together with IL-12 is a strong stimulator for IFN-gamma production. We investigated the relative roles of IL-18 and IL- 12 in protective immunity to C. trachomatis mouse pneumonitis (MoPn) infection using gene knockout (KO) and wild-type (WT) mice. MATERIALS AND METHODS: Mice were intranasally infected with C. trachomatis MoPn and protective immunity was assessed among groups of mice by daily body weight changes, lung growth of MoPn, and histopathological appearances at day 10 postinfection. The corresponding immune responses for each group of mice at the same postinfection time point were evaluated by measuring antigen-specific antibody isotype responses and cytokine profiles. RESULTS: Our results showed that IL-18 deficiency had little or no influence on clearance of MoPn from the lung, although KO mice exhibited slightly more severe inflammatory reactions in lung tissues, as well as reduced systemic and local IFN-gamma production, compared with WT mice. Results with IL-18 KO mice were in sharp contrast to those observed with IL-12 KO mice that showed substantially reduced clearance of MoPn from the lungs, substantial reductions of antigen-specific systemic and lung IFN-gamma production, decreased ratio of MoPn-specific immunoglobulin G (IgG)2a/IgG1, and severe pathological changes in the lung with extensive polymorphonuclear, instead of mononuclear, cell infiltration. Exogenous IL-12 or IL-18 was able to increase IFN-gamma production in IL-18 KO mice; whereas, only exogenous IL-12, but not IL-18, enhanced IFN-gamma production in IL-12 KO mice. Caspase-1 is the key protease for activation of IL-18 precursor into the bioactive form, and caspase-1 KO mice also displayed similar bacterial clearance and body weight loss to that in WT mice at early stages of MoPn infection. This further confirmed that IL-18 was not essential for host defense against chlamydia infection. CONCLUSIONS: These results suggest that IL-12, rather than IL-18, plays the dominant role in the development of protective immunity against chlamydia lung infection, although both cytokines are involved in the in vivo regulation of IFN-gamma production.

Animals↗
PubMed2000

[A case of callosal apraxia without agraphia and acquired stuttering associated with callosal infarction].

We report a 52-year-old right-handed man with cerebral infarction of the right anterior cerebral artery area. The MRI findings showed cerebral infarction in the trunk of the right corpus callosum, although some part of the posterior half of the trunk was spared. Some part of right precuneal gyrus, cingulate gyrus were also involved. The clinical feature of this case is characterized by following two points. First, although callosal apraxia is usually accompanied by agraphia, he showed apraxia with the left hand, but showed no agraphia. Secondary, he showed speech dysfluency mainly characterized by initial syllable repetitions. The nature of this speech dysfluency was determined as acquired stuttering. This case suggests that the pathway for praxis locates distinct portion from that for writing on corpus callosum. We analyzed callosal lesions of previous studies reporting callosal apraxia without agraphia, then compared to that of this case. And we also reviewed acquired stuttering report caused by callosal lesions. Consequently, we suggest that apraxia and stuttering were caused by damage of the trunk of the corpus callosum. While writing was preserved by the intact fibers in the posterior half of the trunk.

Apraxias↗